This project is designed to elucidate mechanisms that translate experience into changes in brain structure that allow adult animals to enhance their behavioral performance. Our model system, foraging-induced growth of the mushoom bodies (insect brain center for learning and memory) in the honey bee, permits nvestigations at the behavioral, cellular, and molecular levels. Our proposal is based on the surprising, but robust, demonstration that treatment of caged bees with a muscarinic agonist, pilocarpine, results in brain plasticity identical to that produced by a week of real foraging experience. We will: 1. determine how signaling via cholinergic pathways is related to foraging-induced increases in the volume of mushroom body neuropil using a novel experience-replacement technique; 2. determine the cellular phenotype of pilocarpine- induced changes in mushroom body neurons (Kenyon cells) using the Golgi technique; and 3. identify genes expressed in the mushroom bodies responsive to signaling via muscarinic pathways using whole bee genome microarrays, and then confirm and extend these results with quantitative RT-PCR and in situ hybridization. The bee provides a superb model system for these studies because appropriate tools, such as a sequenced genome, are now available, and because it is possible to rigorously manipulate the experience of the bee under naturalistic conditions and study effects at the neuroanatomical and molecular levels. The principal significance of this research is that it will reveal how experience is coupled to brain plasticity. Extensive conservation of nervous system function at the molecular level across the animal kingdom makes the results of our investigations on an insect broadly applicable within the field of behavioral development. This research is relevant to public health because experiments that can be efficiently performed using the simpler insect nervous system are likely to reveal how learning changes the brain in all animals, including humans. Such understanding is the first step in the development of therapies to improve human learning after brain damage. Our results will also suggest directions for the development of treatments for the decline in mental function that accompanies human aging.